Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6
By R. Lee, A. Pulin, Min-Jeong Seo, Daniel J Kota, Joni H. Ylostalo, B. Larson, L. Semprun-Prieto, P. Delafontaine, D. Prockop. Cell Stem Cell, 2009
1,807 citations recorded by the source corpus.
SUMMARY Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 × 106 hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. I.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.
Subfields: Genetics, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/8b0578939b377ea0fa821cd483012dad72ec3760
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Citations in the corpus
- Mesenchymal Stem Cells as Therapeutics (2010, neutral): “F or p er so na l u se o nl y. iv Tracking Ti m e af te r i v in je ct io n 1 h 24 h 7 days 30 days <1% ~0% ~0% ~0% <1% ~0% ~0% ~0% <1% ~0% ~0% ~0% <1% ~0% ~0% ~0% <1% ~0% ~0% ~0% <1% ~0% ~0% ~0% Heart 83% 42% <0.01% ~0% ~0% ~0% ~0% ~0% ~0% ~0% <0.1% 0.5% <0.5% ~0% ~0% ~0% ~0% ~0% ~0% ~0% ~0% ~0% <1”
- Mechanisms of mesenchymal stem/stromal cell function (2016, background): “Consistent with their immune-modulatory properties, efficacy with MSC treatment has been demonstrated in a variety of inflammatory models of disease, including arthritis [63], Crohn’s disease [64], multiple sclerosis [65, 66], myocardial infarction [14], diabetes [51, 67], graft versus host disease ”
- Same or Not the Same? Comparison of Adipose Tissue-Derived Versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells (2012, neutral): “Furthermore, there are data that MSCs may exert their therapeutic functions through systemic (endocrine) activity, and this provides an explanation, at least in part, for how intravenously injected MSCs can act on distant injured or diseased tissues [82], as data from animal studies have”
- Mesenchymal stromal cells: new directions. (2012, background): “…6 protein (TSG6) is an immunosuppressive molecule produced by MSCs 712 Cell Stem Cell 10, June 14, 2012 ª2012 Elsevier Inc. that partially recapitulates the hemodynamic improvement after intravenous infusion of the cells following experimental acute myocardial infarction in mice (Lee et al., 2009).”